PROPEL: A Study to Evaluate Administration of SBT101 Gene Therapy in Adult Patients With Adrenomyeloneuropathy (AMN)

Sponsor

SwanBio Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05394064

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1/2 randomized, blinded, dose-escalation study to evaluate the safety and efficacy of intrathecal (IT) administration of SBT101, a recombinant adeno-associated virus serotype 9 (AAV9) containing a functional copy of the human adenosine triphosphate (ATP)-binding cassette transporter subfamily D member 1 (ABCD1; hABCD1) gene, in adult patients with adrenomyeloneuropathy (AMN) aged 18-65 years.

Patients will receive a single dose of SBT101 via IT route (or an imitation procedure) and will be followed for safety and efficacy for 2 years. Patients receiving SBT101 will be followed for an additional 3 years (5 total) for Safety. Patients receiving an imitation procedure will be offered the opportunity to receive SBT101 after 2 years, as data indicate.

Condition or Disease	Intervention/Treatment	Phase
AMN AMN Gene Mutation X-ALD	Genetic: SBT101 Procedure: Imitation Procedure	Phase 1/Phase 2

Detailed Description

The study consists of two parts after infusion of SBT101:

Part 1: A blinded 24-month core study period to evaluate the safety and potential impact of

SBT101 on disease progression. Part 1 will consist of 2 phases:

Phase 1: Dose-Escalation Phase: Two (2) doses of SBT101 (Dose level 1 cohort and Dose Level 2 cohort) will be evaluated to establish the maximum tolerated dose (MTD).

Phase 2: Dose-Expansion Phase: Additional patients will be enrolled to receive SBT101 at the MTD

Part 2: An unblinded 3-year long-term safety follow-up period with annual follow-up visits to evaluate the safety of SBT101 and disease progression.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

3 Cohorts, each with active treatment and imitation procedure3 Cohorts, each with active treatment and imitation procedure

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Maintain masking to all but those are perform the actual procedure

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Randomized, Blinded, Dose-escalation Study to Evaluate the Safety and Efficacy of Intrathecal Administration of AAV9-ABCD1 Gene Therapy (SBT101) in Adult Patients With Adrenomyeloneuropathy

Anticipated Study Start Date :

Jun 30, 2022

Anticipated Primary Completion Date :

Mar 30, 2026

Anticipated Study Completion Date :

Mar 30, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Treatment Patients treated with SBT101	Genetic: SBT101 SBT101 Treatment
Sham Comparator: Imitation Procedure Procedure that mimics treatment with SBT101, but does not infuse anything into the spinal cord	Procedure: Imitation Procedure Procedure that mimics SBT101 infusion, but contains no drug administered Other Names: Sham Procedure

Arm

Intervention/Treatment

Experimental: Active Treatment

Patients treated with SBT101

Genetic: SBT101

SBT101 Treatment

Sham Comparator: Imitation Procedure

Procedure that mimics treatment with SBT101, but does not infuse anything into the spinal cord

Procedure: Imitation Procedure

Procedure that mimics SBT101 infusion, but contains no drug administered

Other Names:

Sham Procedure

Outcome Measures

Primary Outcome Measures

Adverse Events to SBT101 [2 years]
Safety and tolerability of SBT101 administration

Secondary Outcome Measures

Disease progression [2 years]
Characterize disease progression in adults diagnosed with AMN through serial clinical assessments of walking ability measured by 6-Minute Walk Test

Other Outcome Measures

Change in Quality of Life [2 years]
Characterize the change in multiple quality of life parameters over time using questionnaires including the Multiple Sclerosis Quality of Life-54 (MS-QOL)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosed with X-linked adrenoleukodystrophy (ALD), including proven mutation in the ABCD1 gene through confirmatory genetic testing, and supported by elevated circulating VLCFA levels.
Clinical evidence of spinal cord involvement but still able to ambulate independently

Exclusion Criteria:

Evidence of or past diagnosis of inflammatory cerebral disease.
15 years or more have elapsed since the initial onset of myeloneuropathy manifestations such as walking or running difficulties, bladder dysfunction, increased muscular tone, spasticity, weakness, balance problems, etc.
Contraindications for MRI procedure and/or contrast materials.
Contraindication to steroids, sirolimus, tacrolimus, and/or anesthetic medications.
Unstable adrenal function (e.g., untreated or inappropriately treated adrenal insufficiency).
History of diabetes or abnormal fasting plasma glucose (≥126 mg/dL) or hemoglobin A1C ≥6.5%.
Patients who have received a gene therapy.